CI072_MOUSE
ID CI072_MOUSE Reviewed; 481 AA.
AC Q6DFW0; A6PWW3; Q3TJP2; Q3U3D8;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 2.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Guanine nucleotide exchange factor C9orf72 homolog {ECO:0000305};
GN Name=C9orf72 {ECO:0000312|MGI:MGI:1920455};
GN Synonyms=Dennd9 {ECO:0000312|MGI:MGI:1920455},
GN Dennl72 {ECO:0000250|UniProtKB:Q96LT7};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE39453.1}, and
RC NOD {ECO:0000312|EMBL:BAE32850.1};
RC TISSUE=Amnion {ECO:0000312|EMBL:BAE39453.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH RAB1A AND RAB7A, AND SUBCELLULAR LOCATION.
RX PubMed=24549040; DOI=10.1093/hmg/ddu068;
RA Farg M.A., Sundaramoorthy V., Sultana J.M., Yang S., Atkinson R.A.,
RA Levina V., Halloran M.A., Gleeson P.A., Blair I.P., Soo K.Y., King A.E.,
RA Atkin J.D.;
RT "C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal
RT dementia, regulates endosomal trafficking.";
RL Hum. Mol. Genet. 23:3579-3595(2014).
RN [6]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=26408000; DOI=10.1186/s40478-015-0238-7;
RA Atkinson R.A., Fernandez-Martos C.M., Atkin J.D., Vickers J.C., King A.E.;
RT "C9ORF72 expression and cellular localization over mouse development.";
RL Acta Neuropathol. Commun. 3:59-59(2015).
RN [7]
RP ERRATUM OF PUBMED:26408000.
RX PubMed=26727886; DOI=10.1186/s40478-015-0253-8;
RA Atkinson R.A., Fernandez-Martos C.M., Atkin J.D., Vickers J.C., King A.E.;
RL Acta Neuropathol. Commun. 4:2-2(2016).
RN [8]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26044557; DOI=10.1002/ana.24453;
RA Koppers M., Blokhuis A.M., Westeneng H.J., Terpstra M.L., Zundel C.A.,
RA Vieira de Sa R., Schellevis R.D., Waite A.J., Blake D.J., Veldink J.H.,
RA van den Berg L.H., Pasterkamp R.J.;
RT "C9orf72 ablation in mice does not cause motor neuron degeneration or motor
RT deficits.";
RL Ann. Neurol. 78:426-438(2015).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27193190; DOI=10.1186/s40478-016-0324-5;
RA Sullivan P.M., Zhou X., Robins A.M., Paushter D.H., Kim D., Smolka M.B.,
RA Hu F.;
RT "The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to
RT regulate the autophagy-lysosome pathway.";
RL Acta Neuropathol. Commun. 4:51-51(2016).
RN [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=27476503; DOI=10.1111/joa.12526;
RA Ferguson R., Serafeimidou-Pouliou E., Subramanian V.;
RT "Dynamic expression of the mouse orthologue of the human amyotropic lateral
RT sclerosis associated gene C9orf72 during central nervous system development
RT and neuronal differentiation.";
RL J. Anat. 229:871-891(2016).
RN [11]
RP FUNCTION, AND INTERACTION WITH ARF1; ARF6 AND CFL1.
RX PubMed=27723745; DOI=10.1038/nn.4407;
RA Sivadasan R., Hornburg D., Drepper C., Frank N., Jablonka S., Hansel A.,
RA Lojewski X., Sterneckert J., Hermann A., Shaw P.J., Ince P.G., Mann M.,
RA Meissner F., Sendtner M.;
RT "C9ORF72 interaction with cofilin modulates actin dynamics in motor
RT neurons.";
RL Nat. Neurosci. 19:1610-1618(2016).
RN [12]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH SMCR8.
RX PubMed=27875531; DOI=10.1371/journal.pgen.1006443;
RA Ugolino J., Ji Y.J., Conchina K., Chu J., Nirujogi R.S., Pandey A.,
RA Brady N.R., Hamacher-Brady A., Wang J.;
RT "Loss of C9orf72 enhances autophagic activity via deregulated mTOR and TFEB
RT signaling.";
RL PLoS Genet. 12:E1006443-E1006443(2016).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26989253; DOI=10.1126/science.aaf1064;
RA O'Rourke J.G., Bogdanik L., Yanez A., Lall D., Wolf A.J., Muhammad A.K.,
RA Ho R., Carmona S., Vit J.P., Zarrow J., Kim K.J., Bell S., Harms M.B.,
RA Miller T.M., Dangler C.A., Underhill D.M., Goodridge H.S., Lutz C.M.,
RA Baloh R.H.;
RT "C9orf72 is required for proper macrophage and microglial function in
RT mice.";
RL Science 351:1324-1329(2016).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27617292; DOI=10.1126/sciadv.1601167;
RA Yang M., Liang C., Swaminathan K., Herrlinger S., Lai F., Shiekhattar R.,
RA Chen J.F.;
RT "A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in
RT autophagy.";
RL Sci. Adv. 2:E1601167-E1601167(2016).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27412785; DOI=10.1126/scitranslmed.aaf6038;
RA Burberry A., Suzuki N., Wang J.Y., Moccia R., Mordes D.A., Stewart M.H.,
RA Suzuki-Uematsu S., Ghosh S., Singh A., Merkle F.T., Koszka K., Li Q.Z.,
RA Zon L., Rossi D.J., Trowbridge J.J., Notarangelo L.D., Eggan K.;
RT "Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal
RT autoimmune disease.";
RL Sci. Transl. Med. 8:347RA93-347RA93(2016).
RN [16]
RP FUNCTION, AND INTERACTION WITH CALM1.
RX PubMed=30366907; DOI=10.1101/gad.315564.118;
RA Liu Y., Wang T., Ji Y.J., Johnson K., Liu H., Johnson K., Bailey S.,
RA Suk Y., Lu Y.N., Liu M., Wang J.;
RT "A C9orf72-CARM1 axis regulates lipid metabolism under glucose starvation-
RT induced nutrient stress.";
RL Genes Dev. 32:1380-1397(2018).
RN [17]
RP FUNCTION, INTERACTION WITH DLG4, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=31651360; DOI=10.1186/s40478-019-0812-5;
RA Xiao S., McKeever P.M., Lau A., Robertson J.;
RT "Synaptic localization of C9orf72 regulates post-synaptic glutamate
RT receptor 1 levels.";
RL Acta Neuropathol. Commun. 7:161-161(2019).
CC -!- FUNCTION: Component of the C9orf72-SMCR8 complex, a complex that has
CC guanine nucleotide exchange factor (GEF) activity and regulates
CC autophagy (PubMed:27193190, PubMed:27617292). In the complex, C9orf72
CC and SMCR8 probably constitute the catalytic subunits that promote the
CC exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B
CC into their active GTP-bound form, thereby promoting autophagosome
CC maturation (By similarity). The C9orf72-SMCR8 complex also acts as a
CC regulator of autophagy initiation by interacting with the ULK1/ATG1
CC kinase complex and modulating its protein kinase activity
CC (PubMed:27193190, PubMed:27617292). As part of the C9orf72-SMCR8
CC complex, stimulates RAB8A and RAB11A GTPase activity in vitro (By
CC similarity). Positively regulates initiation of autophagy by regulating
CC the RAB1A-dependent trafficking of the ULK1/ATG1 kinase complex to the
CC phagophore which leads to autophagosome formation (By similarity). Acts
CC as a regulator of mTORC1 signaling by promoting phosphorylation of
CC mTORC1 substrates (PubMed:27875531). Plays a role in endosomal
CC trafficking (PubMed:26989253). May be involved in regulating the
CC maturation of phagosomes to lysosomes (PubMed:26989253). Promotes the
CC lysosomal localization and lysosome-mediated degradation of CARM1 which
CC leads to inhibition of starvation-induced lipid metabolism
CC (PubMed:30366907). Regulates actin dynamics in motor neurons by
CC inhibiting the GTP-binding activity of ARF6, leading to ARF6
CC inactivation (PubMed:27723745). This reduces the activity of the LIMK1
CC and LIMK2 kinases which are responsible for phosphorylation and
CC inactivation of CFL1/cofilin, leading to cofilin activation
CC (PubMed:27723745). Positively regulates axon extension and axon growth
CC cone size in spinal motor neurons (PubMed:27723745). Required for SMCR8
CC protein expression and localization at pre- and post-synaptic
CC compartments in the forebrain, also regulates protein abundance of
CC RAB3A and GRIA1/GLUR1 in post-synaptic compartments in the forebrain
CC and hippocampus (PubMed:31651360). Plays a role within the
CC hematopoietic system in restricting inflammation and the development of
CC autoimmunity (PubMed:27412785). {ECO:0000250|UniProtKB:Q96LT7,
CC ECO:0000269|PubMed:26989253, ECO:0000269|PubMed:27193190,
CC ECO:0000269|PubMed:27412785, ECO:0000269|PubMed:27617292,
CC ECO:0000269|PubMed:27723745, ECO:0000269|PubMed:27875531,
CC ECO:0000269|PubMed:30366907, ECO:0000269|PubMed:31651360}.
CC -!- SUBUNIT: Component of the C9orf72-SMCR8 complex, at least composed of
CC C9orf72, SMCR8 and WDR41 (Probable). The complex is formed of two
CC protomers, each individually consisting of one molecule each of
CC C9orf72, SMCR8 and WDR41 (By similarity). The protomers homodimerize
CC via an interaction between C9orf72 (via C-terminus) and SMCR8 (via N-
CC terminus) (By similarity). Within each protomer SMCR8 (via DENN domain)
CC acts as a bridging protein between WDR41 (via C-terminus and N-
CC terminus) and C9orf72 (via C-terminus) (By similarity). The C9orf72-
CC SMCR8 complex associates with the ULK1/ATG1 kinase complex (By
CC similarity). Interacts with ULK1/ATG1 kinase complex members ULK1,
CC ATG13 and RB1CC1 (By similarity). Interacts with SMCR8; the interaction
CC is direct (PubMed:27875531). Interacts with HNRNPA1, HNRNPA2B1 and
CC UBQLN2 (By similarity). Interacts with small Rab GTPase RAB1A; the
CC interaction mediates recruitment of RAB1A to the ULK1/ATG1 kinase
CC complex (PubMed:24549040). Also interacts with small Rab GTPase RAB7A
CC (PubMed:24549040). Interacts with cofilin (PubMed:27723745). Interacts
CC with GTP-binding proteins ARF1 and ARF6 (PubMed:27723745). Interacts
CC with the DLG4/PSD-95 (PubMed:31651360). Interacts with CARM1 (via PH
CC domain-like fold) (PubMed:30366907). {ECO:0000250|UniProtKB:Q96LT7,
CC ECO:0000269|PubMed:24549040, ECO:0000269|PubMed:27723745,
CC ECO:0000269|PubMed:27875531, ECO:0000269|PubMed:30366907,
CC ECO:0000269|PubMed:31651360}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24549040,
CC ECO:0000269|PubMed:26408000, ECO:0000269|PubMed:27476503}. Cytoplasm
CC {ECO:0000269|PubMed:24549040, ECO:0000269|PubMed:26408000,
CC ECO:0000269|PubMed:27476503, ECO:0000269|PubMed:27617292}. Cytoplasm,
CC P-body {ECO:0000250|UniProtKB:Q96LT7}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q96LT7}. Endosome
CC {ECO:0000250|UniProtKB:Q96LT7}. Lysosome
CC {ECO:0000250|UniProtKB:Q96LT7}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q96LT7}. Secreted {ECO:0000269|PubMed:24549040}.
CC Cell projection, axon {ECO:0000250|UniProtKB:Q96LT7}. Cell projection,
CC growth cone {ECO:0000250|UniProtKB:Q96LT7}. Perikaryon
CC {ECO:0000269|PubMed:26408000}. Note=Detected in the cytoplasm of
CC neurons from brain tissue (By similarity). Detected in the nucleus in
CC fibroblasts (By similarity). Associates with cytoplasmic stress
CC granules following cellular stress (By similarity). During
CC corticogenesis, transitions from being predominantly cytoplasmic to a
CC more even nucleocytoplasmic distribution (PubMed:27476503).
CC {ECO:0000250|UniProtKB:Q96LT7, ECO:0000269|PubMed:27476503}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Perikaryon
CC {ECO:0000250|UniProtKB:Q96LT7}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q96LT7}. Presynapse
CC {ECO:0000269|PubMed:31651360}. Postsynapse
CC {ECO:0000269|PubMed:31651360}. Note=Expressed diffusely throughout the
CC cytoplasm and dendritic processes of cerebellar Purkinje cells. Also
CC expressed diffusely throughout the cytoplasm of spinal motor neurons.
CC {ECO:0000250|UniProtKB:Q96LT7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6DFW0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6DFW0-2; Sequence=VSP_059260;
CC -!- TISSUE SPECIFICITY: Expressed in postnatal cerebellum and cortex (at
CC protein level). Neuronal expression is detected in several regions of
CC the adult brain and spinal cord (PubMed:26044557). Prominent expression
CC also observed in embryonic and early postnatal neurons including
CC retinal ganglion cells, sensory neurons in the olfactory epithelium and
CC in dorsal root ganglia, and spinal motor neurons (PubMed:26044557).
CC Expressed in the developing cerebral cortex, cerebellum, olfactory
CC bulb, hippocampus and spinal cord in the embryo and in P0 cortical
CC neurons and astrocytes (PubMed:27476503). Also expressed in non-
CC neuronal tissues such as kidney and tooth (PubMed:26044557). In the
CC spleen, highly expressed in myeloid cells compared to B cell and T cell
CC populations where expression is much lower (PubMed:26989253). In the
CC brain, highly expressed in microglia (PubMed:26989253).
CC {ECO:0000269|PubMed:26044557, ECO:0000269|PubMed:26989253,
CC ECO:0000269|PubMed:27476503}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in the forebrain, including
CC in the glomerular layer of the olfactory bulb (at protein level).
CC {ECO:0000269|PubMed:31651360}.
CC -!- DEVELOPMENTAL STAGE: Expressed in cerebral cortex and hippocampus at
CC embryonic day 18 and postnatal days 1, 7, 14, 28 and 56.
CC {ECO:0000269|PubMed:26408000}.
CC -!- DISRUPTION PHENOTYPE: Decreased life span (PubMed:27875531,
CC PubMed:27412785). However, another report did not observe any effect on
CC life span (PubMed:26989253). Lymph node and spleen enlargement
CC phenotype accompanied by macrophage infiltration (PubMed:27193190,
CC PubMed:27875531, PubMed:26989253, PubMed:27412785). Severe inflammation
CC also observed in liver (PubMed:27193190, PubMed:27412785). Increased
CC total white blood cell count due to a significant increase in the
CC number of circulating neutrophils (PubMed:27412785). Significantly
CC reduced platelet and red blood cell count (PubMed:27412785). Increased
CC levels of autophagy and lysosomal proteins and autophagy defects in the
CC spleen and liver (PubMed:27193190). Impaired activation of MTOR/mTOR
CC (PubMed:27875531). Massive up-regulation of the cell surface receptor
CC Trem2 (PubMed:26989253). Significantly increased levels of a number of
CC inflammatory chemokines and cytokines (PubMed:26989253,
CC PubMed:27412785). Increased levels of autoantibodies indicative of an
CC autoimmune phenotype (PubMed:27412785). Normal weight gain,
CC sensorimotor coordination, limb strength, femoral motor and sensory
CC axon counts, and muscle electrophysiology (PubMed:26989253).
CC Conditional knockout in neurons and glial cells results in
CC significantly reduced body weight but does not induce motor neuron
CC degeneration, defects in motor function or altered survival
CC (PubMed:26044557). SMCR8 protein expression is abolished in pre- and
CC post-synaptic compartments in forebrain synapses (PubMed:31651360).
CC RAB3A expression levels are increased in synaptosomes, however are
CC decreased in post-synaptic compartments of the forebrain and in the
CC hippocampus (PubMed:31651360). GRIA1/GLUR1 protein levels are increased
CC in forebrain post-synaptic compartments and in the hippocampus
CC (PubMed:31651360). {ECO:0000269|PubMed:26044557,
CC ECO:0000269|PubMed:26989253, ECO:0000269|PubMed:27193190,
CC ECO:0000269|PubMed:27412785, ECO:0000269|PubMed:27875531,
CC ECO:0000269|PubMed:31651360}.
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DR EMBL; AK154817; BAE32850.1; -; mRNA.
DR EMBL; AK167354; BAE39453.1; -; mRNA.
DR EMBL; AL831776; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466538; EDL05455.1; -; Genomic_DNA.
DR EMBL; CH466538; EDL05456.1; -; Genomic_DNA.
DR EMBL; BC076612; AAH76612.1; -; mRNA.
DR CCDS; CCDS38708.1; -. [Q6DFW0-1]
DR RefSeq; NP_001074812.1; NM_001081343.1. [Q6DFW0-1]
DR RefSeq; XP_006538355.1; XM_006538292.3. [Q6DFW0-1]
DR RefSeq; XP_006538356.1; XM_006538293.3. [Q6DFW0-1]
DR AlphaFoldDB; Q6DFW0; -.
DR SMR; Q6DFW0; -.
DR ComplexPortal; CPX-3962; C9orf72-SMCR8 complex. [Q6DFW0-1]
DR IntAct; Q6DFW0; 1.
DR MINT; Q6DFW0; -.
DR STRING; 10090.ENSMUSP00000103762; -.
DR iPTMnet; Q6DFW0; -.
DR PhosphoSitePlus; Q6DFW0; -.
DR SwissPalm; Q6DFW0; -.
DR MaxQB; Q6DFW0; -.
DR PaxDb; Q6DFW0; -.
DR PRIDE; Q6DFW0; -.
DR Antibodypedia; 10609; 259 antibodies from 32 providers.
DR Ensembl; ENSMUST00000084724; ENSMUSP00000081775; ENSMUSG00000028300. [Q6DFW0-2]
DR Ensembl; ENSMUST00000108127; ENSMUSP00000103762; ENSMUSG00000028300. [Q6DFW0-1]
DR GeneID; 73205; -.
DR KEGG; mmu:73205; -.
DR UCSC; uc008sgv.1; mouse.
DR UCSC; uc008sgw.1; mouse. [Q6DFW0-1]
DR CTD; 203228; -.
DR MGI; MGI:1920455; C9orf72.
DR VEuPathDB; HostDB:ENSMUSG00000028300; -.
DR eggNOG; ENOG502QSST; Eukaryota.
DR GeneTree; ENSGT00390000005644; -.
DR InParanoid; Q6DFW0; -.
DR OMA; IFGRSFY; -.
DR OrthoDB; 1434762at2759; -.
DR TreeFam; TF313315; -.
DR BioGRID-ORCS; 73205; 4 hits in 71 CRISPR screens.
DR PRO; PR:Q6DFW0; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q6DFW0; protein.
DR Bgee; ENSMUSG00000028300; Expressed in facial nucleus and 263 other tissues.
DR ExpressionAtlas; Q6DFW0; baseline and differential.
DR Genevisible; Q6DFW0; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:1990316; C:Atg1/ULK1 kinase complex; ISO:MGI.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0090543; C:Flemming body; ISO:MGI.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0044304; C:main axon; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:1902774; P:late endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0045920; P:negative regulation of exocytosis; IC:ComplexPortal.
DR GO; GO:1904425; P:negative regulation of GTP binding; IMP:UniProtKB.
DR GO; GO:0050777; P:negative regulation of immune response; IC:ComplexPortal.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISS:UniProtKB.
DR GO; GO:0110053; P:regulation of actin filament organization; IMP:UniProtKB.
DR GO; GO:2000785; P:regulation of autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP:UniProtKB.
DR GO; GO:1903432; P:regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; ISS:UniProtKB.
DR InterPro; IPR027819; C9orf72.
DR PANTHER; PTHR31855; PTHR31855; 1.
DR Pfam; PF15019; C9orf72-like; 1.
DR PROSITE; PS51835; DENN_C9ORF72; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Endosome; Guanine-nucleotide releasing factor;
KW Lysosome; Nucleus; Reference proteome; Secreted; Synapse.
FT CHAIN 1..481
FT /note="Guanine nucleotide exchange factor C9orf72 homolog"
FT /id="PRO_0000089712"
FT DOMAIN 23..194
FT /note="uDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT DOMAIN 200..343
FT /note="cDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT DOMAIN 370..464
FT /note="dDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT REGION 461..481
FT /note="Required for the homodimerization of the C9orf72-
FT SMCR8 complex"
FT /evidence="ECO:0000250|UniProtKB:Q96LT7"
FT VAR_SEQ 421..481
FT /note="Missing (in isoform 2)"
FT /id="VSP_059260"
FT CONFLICT 373
FT /note="R -> T (in Ref. 1; BAE39453)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 481 AA; 54278 MW; 5769553C2772049C CRC64;
MSTICPPPSP AVAKTEIALS GESPLLAATF AYWDNILGPR VRHIWAPKTD QVLLSDGEIT
FLANHTLNGE ILRNAESGAI DVKFFVLSEK GVIIVSLIFD GNWNGDRSTY GLSIILPQTE
LSFYLPLHRV CVDRLTHIIR KGRIWMHKER QENVQKIVLE GTERMEDQGQ SIIPMLTGEV
IPVMELLASM KSHSVPEDID IADTVLNDDD IGDSCHEGFL LNAISSHLQT CGCSVVVGSS
AEKVNKIVRT LCLFLTPAER KCSRLCEAES SFKYESGLFV QGLLKDATGS FVLPFRQVMY
APYPTTHIDV DVNTVKQMPP CHEHIYNQRR YMRSELTAFW RATSEEDMAQ DTIIYTDESF
TPDLNIFQDV LHRDTLVKAF LDQVFHLKPG LSLRSTFLAQ FLLILHRKAL TLIKYIEDDT
QKGKKPFKSL RNLKIDLDLT AEGDLNIIMA LAEKIKPGLH SFIFGRPFYT SVQERDVLMT
F
